Vitamin D status and blood group among severe COVID-19 patients

Abstract

Objective:

Prognosis of COVID-19 infection has been indicated to be associated with vitamin D status and ABO blood group. However, owing to discrepancies and an increased number of cases globally, the findings remain unclear. This study aimed to evaluate the association between vitamin D and ABO blood group systems in patients with severe COVID-19.

Methods:

In this cross-sectional study, COVID-19 patients referred to two hospitals in the capital of Iran, Tehran, admitted to the ICU ward due to the severity of COVID-19 were evaluated. Serum vitamin D and ABO levels were evaluated in these patients. The data obtained were statistically analyzed using SPSSv24.

Results:

Of 305 patients, 33.1% patients had O+ blood type, 27.8% had A+ blood type and 22.4% had B+ blood type. Vitamin D deficiency was significantly associated with a mortality rate among these patients, P<0.05. The blood group of the patients was not correlated with mortality. Thirty-seven percent of the patients in the study died because of COVID-19.

Conclusion:

In our study population, mortality due to COVID-19 was significantly associated with vitamin D deficiency but not the ABO blood group. We recommend further studies in this regard that include more variable and detailed biochemical analysis.

Introduction

Highlights

• Prognosis of COVID-19 infection has been indicated to be associated with vitamin D status and ABO blood group.

• However, there, due to discrepancies and increased number of cases globally, the findings remain unclear.

• In our study population, mortality due to COVID-19 patients was significantly associated with vitamin D deficiency but not ABO blood group.

• We recommend further studies in this regard, including more variable and detailed biochemical analysis.

SARS-CoV-2 causing COVID-19 has impacted millions worldwide. Although the infection primarily affects the lungs, multisystem manifestation is increasingly reported^1,2. Individuals with comorbidities such as cardiovascular disease, diabetes, obesity, and lung diseases have a poor prognosis for the infection and are more vulnerable to severe disease^3,4.

Vitamin D is known to regulate inflammatory response in lungs via renin-angiotensin system (RAS). Animal studies have shown that hyperactivation of the RAS^5,6 is likely to be particularly relevant to the prognosis of COVID-19. A number of clinical studies have shown that mortality rate is higher among vitamin D-deficient patients than among those with normal levels of vitamin D⁷, owing to its role as an immunomodulator^8,9. The protective role of vitamin D supplementation in reducing the risk of mortality and admission to ICUs in patients with COVID-19 has been shown in a meta-analysis and trial sequential analysis¹⁰. Although in this study only five randomized clinical trials were suitable for analysis, the results suggest a clear association between vitamin D administration and a decreased risk of death and ICU admission. However, further studies are needed to confirm the positive results regarding the protective role of vitamin D in mortality risk. These findings highlight the potential importance of vitamin D supplementation as a possible preventive measure against severe COVID-19 outcomes, particularly for individuals with vitamin D deficiency.

ABO blood group plays an important role in the pathogenesis of diseases such as cancer and cardiovascular diseases and is correlated with the risk of certain infections^11,12. Preliminary data from China, following the pandemic, showed that certain types of blood groups are likely to increase the risk of COVID-19 and may be associated with a poor prognosis of the disease^13,14. The blood group system can provide a binding site for microorganisms and parasites, as receptors or co-receptors and thus contribute to infection¹⁵. Variations in the expression of blood group antigens on red blood cells can increase or decrease the risk of certain infections by cell signalling and facilitating cellular uptake and adhesion^16,17.

Vitamin D and blood groups have been studied in relation to COVID-19 because both have been found to play a role in immune function and inflammation, which are important factors in the severity and outcomes of COVID-19. Vitamin D is known to regulate inflammatory response in the lungs via the RAS and has been shown to have a protective role in reducing the risk of mortality and admission to intensive care units in patients with COVID-19. On the other hand, ABO blood group has been found to be correlated with the risk of certain infections, including COVID-19, and may provide a binding site for microorganisms and parasites, contributing to infection. Therefore, studying both vitamin D status and ABO blood group in relation to COVID-19 can provide important insights into the pathogenesis and potential preventive measures against severe COVID-19 outcomes.

Owing to the multisystem manifestation of COVID-19 and discrepancies in the findings regarding the prognosis of the infection, status of vitamin D and ABO blood group may vary based on the population and other disease-related factors. Therefore, we conducted this study in two centres in Tehran, Iran, where Iranians presented with COVID-19 were evaluated for the prognosis of COVID-19 based on vitamin D status and ABO blood group.

Methods

This cross-sectional study was conducted in (Shohadaye Tajrish Hospital and Bu Ali Hospital in Tehran) where patients referred to the centre with COVID-19 were evaluated for their blood type and vitamin D levels. Written consent was obtained from all patients prior to their inclusion in the study. Inclusion criteria included completely unvaccinated patients with positive test for polymerase chain reaction, patients admitted with severe COVID admitted to the ICU age group 18–80 years, no vitamin D consumption in the last 6 months and no disease that affects the metabolism of vitamin D (bone-related or thyroid-related). Individuals with a known history of liver or kidney disease, the presence of malignancy, or a history of recent acute illness and those consuming vitamin D supplements were excluded from the study. Pregnant and lactating women were excluded from this study.

Simple sampling was used to select participants for both the case and control groups in this study. We identified the ABO blood group of each patient by using their medical history. The serum level of vitamin D and the blood type of the hospitalized COVID-19 patients was checked and their correlation with the outcome of the disease was assessed. Serum levels of 25-hydroxyvitamin D were measured using a radioimmunoassay (Biosource).

Data were computerized and statistically analyzed using SPSSv24 (IBM). Descriptive data are presented as frequencies and percentages. The Fisher test and independent t-test were used for comparative analysis. P<0.05 was statistically significant.

This study was approved by the Research Ethics Board of (Shohadaye Tajrish Hospital and Bu Ali Hospital in Tehran).

The unique identifying number is researchregistry7860.

The work has been reported in line with the STROCSS criteria¹⁸.

Results

Of 305 patients included in the study, 33.1% patients were O+, 27.8% were A+ blood type and 22.4% had B+ blood type. An Independent t-test was used to examine the relationship between serum vitamin D and mortality rate. There is a significant relationship between these two variables P<0.05.

The Fisher test was used to investigate the relationship between the blood group variable and mortality rate. The result showed no significant relationship between the two variables, P>0.05.

A descriptive table of patient mortality showed that 37% of patients died of COVID-19.

The χ² test showed that there was no significant association between blood type and gender (P value = 0.20 and χ² value=9.85). Also, the blood group was not significantly associated with mortality in these patients (P value=0.4=64 and χ² value= 0.2) (Fig. 1).

Figure 1.

Blood type and vitamin D level grouped by final outcome (dead or alive).

Results of the one-sample t-test showed that there was a significant difference between vitamin D levels in our study population and healthy individuals.

The results also showed that vitamin D and age, sex and vitamin D, and mortality and vitamin D were significantly correlated, with P value less than 0.001, P value less than 0.01, and P value less than 0.001, respectively (Fig. 2). However, age and sex in our study population were not significantly correlated variables, with P value =0.47(Fig. 3).

Figure 2.

Blood type and vitamin D level grouped by sex (male or female).

Figure 3.

Blood type and age grouped by final outcome (dead or alive).

One-way F-test (ANOVA) showed that there was no significant association between blood types and age and vitamin D levels, P value= 0.28 and 0.15, respectively (Fig. 4).

Figure 4.

Pairplot diagram of age and vitamin D level grouped by sex (A) and final outcome (B). Pairplot diagram of age and vitamin D level grouped by blood type.

Discussion

The findings of our study showed that vitamin D level among COVID-19 patients is significantly associated with mortality; however, this might be true for the blood group. Reduced vitamin D levels are more common among patients who died of COVID-19, admitted to ICU, owing to severe COVID-19.

Lung inflammation and fibrosis indicating the severity of the disease are associated with increased production of inflammatory cytokines such as IL-1b, and IL-18 and subsequent activation of macrophages and Th1 cells. Aged and immunocompromised patients are reported with a greater risk of developing the disease. Vitamin D is known as an anti-inflammatory immunomodulator. It inhibits the production of inflammatory cytokines interleukin-1 alpha, interleukin-1 beta, and tumor necrosis factor alpha, due to overexpression of Th1 cytokines^19–21.

In a prospective observational study Jain, Chaurasia²² evaluated vitamin D levels along with inflammatory markers among COVID-19 patients. The findings of the study showed that severely ill COVID-19 patients are vitamin D deficient, compared to asymptomatic COVID-19 patients. These patients also had relatively higher inflammatory markers like TNFα, IL-6, and serum ferritin and a greater risk of mortality. The study concluded that dysregulation of immunity mediated by vitamin D deficiency could add to the severity of COVID-19. Supplementation of vitamin D in a high-risk group is, therefore, recommended. Additionally, patients who are deficient in vitamin D and vitamin D supplements do not increase serum levels of vitamin D in them, and are at a greater risk of being COVID-19-positive²³. Such studies have indicated the protective role of vitamin D against infection²⁴.

In 2005, a study by Cheng, Cheng²⁵ reported that blood group O has greater susceptibility to severe acute respiratory syndrome coronavirus infection. Similarly, a recent study showed that blood group O is associated with an increased risk of norovirus infection²⁶. On the contrary, anti-A antibodies inhibit the binding of spike S protein of SARS-CoV-2 to angiotensin-converting enzyme receptors. Therefore, a number of studies have concluded that blood group O has the lowest susceptibility to COVID-19 whereas, blood group A has the highest. Furthermore, genome-wide associated study has also shown that polymorphism of ABO genes inhibits SARS-CoV-2 infection²⁷. Muñiz-Diaz, Llopis²⁸ conducted a retrospective study on COVID-19 patients to evaluate the role of the ABO blood group in the infection. The findings of the study concluded that blood group O and A is associated with reduced and increased risk of COVID-19 infection. Additionally, the mortality rate is higher in blood group A patients. A study conducted on 19 patients in India showed that blood group AB had the greatest risk of COVID-19 infection, and blood group B had the least²⁹. A recent systematic review and meta-analysis also concluded that the risk of COVID-19 infection is higher in blood groups A and B and lowest in O group³⁰. The findings of our study are not parallel with those reported in the aforementioned research. Almadhi, Abdulrahman³¹ concluded that the highest risk was associated with the B group and the lowest was that with the AB group. However, ABO antibodies were not associated with the risk of infection or the prognosis of the disease. Latz, DeCarlo³² showed that blood group A is not associated with the risk of infection whereas, B and AB have increased risk, and group O has reduced risk of COVID-19. Overall, ABO group was not the predictor of intubation, death, or increased serum inflammatory markers.

Acquiring data from patients in critical condition was challenging for which we used information provided by next of kin. Some of the patients were unsure if vitamin D was part of their everyday supplements, and were therefore excluded from the study. This also compromised our sample size.

Based on the current understanding, there is emerging evidence that ABO blood group may have an impact on the susceptibility, severity, and clinical outcomes of COVID-19³³. Some studies have reported that blood group A is associated with an increased risk of developing severe COVID-19, while blood group O is associated with a decreased risk^34,35. There are several possible mechanisms for how ABO blood group might affect COVID-19. One hypothesis is that the ABO antigen may influence the binding of SARS-CoV-2 virus to the host cells, and thereby affect viral entry and replication³⁶. Blood group A individuals have been found to have higher levels of ACE2 receptor, which is the receptor used by the virus to enter the host cells. On the other hand, blood group O individuals have been found to have lower levels of ACE2 receptor, which might explain their reduced susceptibility to COVID-19. Another possible mechanism is that the ABO antigen may modulate the host immune response to the virus. Blood group A individuals have been found to have higher levels of pro-inflammatory cytokines, which may contribute to the severity of the disease. Blood group O individuals, on the other hand, have been found to have higher levels of anti-inflammatory cytokines, which may confer protection against severe COVID-19³⁷. Overall, more research is needed to fully understand the role of ABO blood group in COVID-19 susceptibility, severity, and clinical outcomes. However, these findings suggest that ABO blood group may be an important factor to consider in the risk stratification and management of COVID-19 patients.

Study strengths and limitations

The strengths of this study are the sample size and the almost evenly distributed number of samples in each class. There are also certain limitations. This study included random subjects, so the results do not apply to other age groups and individuals of other ethnic origins. Thus, it could be assumed that the participants are not representative of all populations.

Future perspective

This article provides some data on the association between Vitamin D status and ABO blood group among severe COVID-19 patients and finally its correlation with mortality. It appears that we will have to continue dealing with Covid-19 and discover new ways to lessen its harm. Our research offers insights into the positive association of vitamin D deficiency with poor prognosis and mortality of COVID-19. These associations between COVID-19 mortality and vitamin D deficiency suggest a possible way in the future to lessen its mortality. Nevertheless, there is a growing demand for greater study in this field.

Conclusion

Our results suggest that deficiency of vitamin D is positively associated with poor prognosis and mortality of COVID-19, however, ABO blood group might not be an effective predictor of COVID-19 outcomes.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the Research Ethics Board of Tehran Islamic Azad University of Medical Sciences, Tehran, Iran (IR.IAU.PS.REC.1400.315).

Consent

From the under 16 years old was given by a parent or legal guardian. Written informed consent was obtained from the patient for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

Source of funding

No funding was secured for this study.

Author contribution

M.A.: conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript. F.G.: designed the data collection instruments, collected data, carried out the initial analyses, and reviewed and revised the manuscript. R.B.: coordinated and supervised data collection, and critically reviewed the manuscript for important intellectual content.

Conflicts of interest disclosure

All authors declare there are no conflicts of interest.

Research registration unique identifying number (UIN)

The unique identifying number is researchregistry7860. https://www.researchregistry.com/browse-the-registry#home/registrationdetails/626d6ffc40dfb5001effe48b/

Guarantor

Mohamad Aryafar.

Provenance and peer review

Not commissioned, externally peer-reviewed.

Availability of data and material

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.